Drosophila and vertebrate casein kinase Idelta exhibits evolutionary conservation of circadian function.
Mutations lowering the kinase activity of Drosophila Doubletime (DBT) and vertebrate casein kinase Iepsilon/delta (CKIepsilon/delta) produce long-period, short-period, and arrhythmic circadian rhythms. Since most ckI short-period mutants have been isolated in mammals, while the long-period mutants have been found mostly in Drosophila, lowered kinase activity may have opposite consequences in flies and vertebrates, because of differences between the kinases or their circadian mechanisms. However, the results of this article establish that the Drosophila dbt mutations have similar effects on period (PER) protein phosphorylation by the fly and vertebrate enzymes in vitro and that Drosophila DBT has an inhibitory C-terminal domain and exhibits autophosphorylation, as does vertebrate CKIepsilon/delta. Moreover, expression of either Drosophila DBT or the vertebrate CKIdelta kinase carrying the Drosophila dbt(S) or vertebrate tau mutations in all circadian cells leads to short-period circadian rhythms. By contrast, vertebrate CKIdelta carrying the dbt(L) mutation does not lengthen circadian rhythms, while Drosophila DBT(L) does. Different effects of the dbt(S) and tau mutations on the oscillations of PER phosphorylation suggest that the mutations shorten the circadian period differently. The results demonstrate a high degree of evolutionary conservation of fly and vertebrate CKIdelta and of the functions affected by their period-shortening mutations.
Fan
Jin-Yuan
JY
Division of Molecular Biology and Biochemistry, University of Missouri, Kansas City, Missouri 64110, USA.
Preuss
Fabian
F
Muskus
Michael J
MJ
Bjes
Edward S
ES
Price
Jeffrey L
JL
D000818:Animals; D030801:Animals, Genetically Modified; D048149:Casein Kinase 1 epsilon / Q000737:chemistry / Q000378:metabolism*; D048148:Casein Kinase Idelta / Q000737:chemistry / Q000378:metabolism*; D002940:Circadian Rhythm; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D019143:Evolution, Molecular; D005838:Genotype; D007527:Isoenzymes / Q000378:metabolism; D009043:Motor Activity; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D056950:Period Circadian Proteins; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D014981:Xenopus / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
D029721:Drosophila Proteins; D007527:Isoenzymes; D050505:Mutant Proteins; D009687:Nuclear Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; C113519:dco protein, Drosophila; D016875:tau Proteins; D048149:Casein Kinase 1 epsilon; D048148:Casein Kinase Idelta; D010749:Phosphoprotein Phosphatases